2′-amino-1-benzyl-5′-hydroxy-5-methoxy-2,6′-dioxo-8′-phenyl-6′H-spiro[indoline-3,4′- pyrano[3,2-g]chromene]-3′‑carbonitrile

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 2′-amino-1-benzyl-5′-hydroxy-5-methoxy-2,6′-dioxo-8′-phenyl-6′H-spiro[indoline-3,4′- pyrano[3,2-g]chromene]-3′‑carbonitrile
• 英文别名: 2'-Amino-1-benzyl-5'-hydroxy-5-methoxy-2,6'-dioxo-8'-phenylspiro[indole-3,4'-pyrano[3,2-g]chromene]-3'-carbonitrile；2'-amino-1-benzyl-5'-hydroxy-5-methoxy-2,6'-dioxo-8'-phenylspiro[indole-3,4'-pyrano[3,2-g]chromene]-3'-carbonitrile
• 化学式: C₃₄H₂₃N₃O₆
• 分子量: 569.573
• InChiKey: HUAADGARXCMTME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  43
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1H-吲哚-2,3-二酮,5-甲氧基-1-(苯基甲基)- 在 calcium hydroxide 作用下， 以 甲醇 为溶剂， 反应 8.17h， 生成 2′-amino-1-benzyl-5′-hydroxy-5-methoxy-2,6′-dioxo-8′-phenyl-6′H-spiro[indoline-3,4′- pyrano[3,2-g]chromene]-3′‑carbonitrile
  参考文献：
  名称：

  Design, synthesis and evaluation of structurally diverse chrysin-chromene-spirooxindole hybrids as anticancer agents

  摘要：

  A series of structurally diverse chrysin-chromene-spirooxindole hybrids were designed, synthesized via a Knoevenagel/Michael/cyclization of chrysin and isatylidene malononitrile derivatives through utilizing a hybrid pharmacophore approach. The newly synthesized compounds were evaluated for their in vitro anticancer activity, and most of the compounds showed stronger anti-proliferative activity than parent compound chrysin. In particular, compound 3e had the highest cytotoxicity towards A549 cells (IC50 = 3.15 +/- 0.51 mu M), and had better selectivity in A549 cells and normal MRC-5 cells. Furthermore, compound 3e could significantly inhibit the proliferation and migration of A549 cells in a dose-dependent manner, as well as induce the apoptosis possibly through mitochondria-mediated caspase-3/8/9 activation and multi-target co-regulation of the p53 signaling pathway. Thus, our results provide in vitro evidence that compound 3e may be a potential candidate for the development of new anti-tumour drugs.

  DOI：

  10.1016/j.bmc.2019.115109

文献信息

• Design, synthesis and evaluation of structurally diverse chrysin-chromene-spirooxindole hybrids as anticancer agents
  作者：Wen-Hui Zhang、Shuang Chen、Xiong-Li Liu、Ting-Ting Feng、Wu-De Yang、Ying Zhou

  DOI：10.1016/j.bmc.2019.115109

  日期：2019.11

  A series of structurally diverse chrysin-chromene-spirooxindole hybrids were designed, synthesized via a Knoevenagel/Michael/cyclization of chrysin and isatylidene malononitrile derivatives through utilizing a hybrid pharmacophore approach. The newly synthesized compounds were evaluated for their in vitro anticancer activity, and most of the compounds showed stronger anti-proliferative activity than parent compound chrysin. In particular, compound 3e had the highest cytotoxicity towards A549 cells (IC50 = 3.15 +/- 0.51 mu M), and had better selectivity in A549 cells and normal MRC-5 cells. Furthermore, compound 3e could significantly inhibit the proliferation and migration of A549 cells in a dose-dependent manner, as well as induce the apoptosis possibly through mitochondria-mediated caspase-3/8/9 activation and multi-target co-regulation of the p53 signaling pathway. Thus, our results provide in vitro evidence that compound 3e may be a potential candidate for the development of new anti-tumour drugs.